It is a common desire to achieve and preserve a youthful appearance as a common denominator of beauty. Over time, however, the skin starts lose its youthful appearance, especially in the face. The most common esthetic signs of facial aging include visibility of skin wrinkles, deep nasolabial folds, glabellar lines, marionette lines, buccal commissures, and perioral wrinkles.
These aging changes are often treated by the injection of dermal fillers to increase the tissue volume. Currently, there are numerous dermal fillers available, which can be broadly classified into two categories. The first category of fillers provides a long-term effect by creating volume and includes fillers such as crosslinked hyaluronic acid (HA) fillers. The second category of fillers provides a long-term effect by inducing neocollagenesis. The best-known and widely used example is Radiesse®, which comprises calcium hydroxyapatite microspheres, a gel carrier of carboxymethyl cellulose (CMC) and glycerin.
Ideal dermal fillers should be biocompatible, have a low adverse event profile, and provide a reasonably long-lasting persistence (longevity), an effective volumizing capacity and ease of injection. HA-based fillers offer many of these desirable properties of dermal fillers. Since HA is found in almost all species, it has no antigenicity and exhibits excellent tolerance. Furthermore, the crosslinking of HA allows the production of crosslinked HA products that have a good lifting capacity and are stable for more than 12 months up to two years.
A major drawback of HA-based fillers is, however, that they are often difficult to inject. For this reason, non-crosslinked HA (“free” HA) is commonly added as a lubricant to ease injection. Unfortunately, the desired decrease of extrusion force that is caused by the addition of free HA compromises other desirable physical properties of the gel. In particular, the G Prime (G′) parameter is lowered, thereby resulting in a reduced volumizing effect, and the dynamic viscosity is decreased.
Radiesse® is a dermal filler that also provides desirable characteristics of a dermal filler, including acceptable longevity, biocompatibility, and a good capacity to create volume. When injected, the small calcium hydroxyapatite microspheres act as a scaffold that promotes new tissue formation similar to its surrounding environment. However, since the CMC carrier of Radiesse® is quickly absorbed in vivo (in about 3 months), there is a potential and transient decrease of the filling effect since neocollagenesis may not be synchronized with CMC elimination. Furthermore, there is no antidote (reversal agent) available for CMC that would allow for a partial correction after filler application.
European patent No. 1 080 698, filed in 1993, discloses an injectable soft tissue augmentation material comprising finely divided ceramic particles (e.g., CaHA) and covers inter alia, Radiesse®. In addition, WO 2014/056723 describes a viscoelastic gel comprising crosslinked HA at a concentration of between 1% and 4% (w/v) and hydroxyapatite particles at a concentration of between 10% and 70% (w/v).